The goal of this proposal is to develop a new, groundbreaking technology for the rapid identification of ligands for proteins. Every year, the pharmaceuticals industry loses about $3 billion by targeting genes/proteins wrongfully identified as the cause of disease. In the past decade, thousands of new genes/proteins with a potential role in disease have been identified. Simultaneously, millions of small molecule ligands have been generated in pharmaceutical libraries with little knowledge on their binding potential to these novel gene/protein targets. Potentia has developed a technology that will pave the way towards the matching of these ligands with new potential drug targets. Intelligent access to these libraries of ligands will generate a wealth of knowledge on disease mechanisms that is deemed to revolutionize the process of gene/protein validation in the drug industry. Potentia's technology is unique in its capacity to circumvent the inherent 'slowness' of analyzing molecules in solution. Proteins are immobilized on the tip of an atomic force microscope and then exposed to arrays of biosensors. Each biosensor is individually functionalized with a different small molecule ligand, resulting in Potentia's groundbreaking screening platform. The first aim of this proposal will be to eliminate background noise when functionalizing specialized biosensors with ligands in order to generate sensors for protein binding. The second aim will be to show that an atomic force microscope tip can be used as a bias electrode to gate our specialized biosensors. The third aim will be to determine whether it is possible to retrieve quantitative information from a binding event when using an atomic force microscope tip as a 'robotic arm' to bring a protein in contact with a ligand-coated biosensor. The success of this proposal will generate intelligence on millions of small molecule-protein interactions, generating unprecedented insight in the various gene/protein pathways and their role in disease.